Background: Myocarditis is a rare but potentially fatal complication of BRAF/MEK inhibitor therapy. Early detection through vigilant monitoring is crucial. Case Summary: A 35-year-old woman with stage IIIB melanoma treated with adjuvant trametinib and dabrafenib suffered a cardiac arrest due to refractory ventricular fibrillation. Coronary angiography excluded culprit lesions. Despite intensive management and extracorporeal life support, the patient exhibited irreversible multiorgan failure and died. A postmortem examination revealed massive biventricular and septal lymphohistiocytic myocarditis. Discussion: BRAF/MEK inhibitors have been demonstrated to enhance survival outcomes in melanoma. However, there exists a potential for cardiotoxic events, including myocarditis, which can be severe albeit infrequent. To date, only isolated cases of fatal myocarditis have been reported. This case highlights the importance of systematic cardiac surveillance, even in asymptomatic patients. Take-Home Messages: Fulminant myocarditis is a rare but life-threatening adverse event of BRAF/MEK inhibitor therapy. Multimodal cardiac evaluation is strongly recommended.
